Preliminary observations have suggested that the cyclic nucleotides might be important in the regulation of normal and malignant tissue growth, but measurements of the levels of cAMP and cGMP in growing cells have produced inconsistent results. Recent immunohistochemical studies of the cyclic nucleotides indicated that both cAMP and cGMP exist in discrete loci within cells raising the possibility that important changes in cyclic nucleotide concentrations might occur in critical cell loci which might not be reflected in measurements of the total tissue content of these nucleotides. We are investigating the changes in cyclic nucleotides in growing and differentiating tissue immunohistochemically by the double antibody immunofluorescent technique. Several models of tissue growth and differentiation are to be examined for the changing pattern of distribution of the nucleotides. Previous studies have shown that during the rat estrus cycle, cells lining the fallopian tube demonstrate a series of morphologic changes suggesting DNA transcription, and synthesis and secretion of a glycoprotein. The patterns of distribution of the cyclic nucleotides during the critical phases of this cycle are to be investigated. Earlier studies have shown that cGMP exists in discrete intranuclear loci. The functional significance of these loci is unknown. Preliminary studies suggest that they are aggregates of DNA. Further studies are planned to determine their functional significance. additional studies are also planned to determine the changing pattern of cyclic nucleotides during the different phases of the cell cycle.